* The Cholinergic Drug Pyridostigmine Alleviates Inflammation During LPS-Induced Acute Respiratory Distress Syndrome.
- Acute respiratory distress syndrome (ARDS) is a critical illness complication that is associated with high mortality. ARDS is documented in severe cases of COVID-19. No effective pharmacological treatments for ARDS are currently available. Dysfunctional immune responses and pulmonary and systemic inflammation are characteristic features of ARDS pathogenesis. Recent advances in our understanding of the regulation of inflammation point to an important role of the vagus-nerve-mediated inflammatory reflex and neural cholinergic signaling. We examined whether pharmacological cholinergic activation using a clinically approved (for myasthenia gravis) cholinergic drug, the acetylcholinesterase inhibitor pyridostigmine alters pulmonary and systemic inflammation in mice with lipopolysaccharide (LPS)-induced ARDS. Male C57Bl/6 mice received one intratracheal instillation of LPS or were sham manipulated (control). Both groups were treated with either vehicle or pyridostigmine (1.5 mg/kg twice daily, 3 mg/day) administered by oral gavage starting at 1 h post-LPS and euthanized 24 h after LPS administration. Other groups were either sham manipulated or received LPS for 3 days and were treated with vehicle or pyridostigmine and euthanized at 72 h. Pyridostigmine treatment reduced the increased total number of cells and neutrophils in the bronchoalveolar lavage fluid (BALF) in mice with ARDS at 24 and 72 h. Pyridostigmine also reduced the number of macrophages and lymphocytes at 72 h. In addition, pyridostigmine suppressed the levels of TNF, IL-1β, IL-6, and IFN-γ in BALF and plasma at 24 and 72 h. However, this cholinergic agent did not significantly altered BALF and plasma levels of the anti-inflammatory cytokine IL-10. Neither LPS nor pyridostigmine affected BALF IFN-γ and IL-10 levels at 24 h post-LPS. In conclusion, treatments with the cholinergic agent pyridostigmine ameliorate pulmonary and systemic inflammatory responses in mice with endotoxin-induced ARDS. Considering that pyridostigmine is a clinically approved drug, these findings are of substantial interest for implementing pyridostigmine in therapeutic strategies for ARDS.
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Overview of verb reduce
The verb reduce has 20 senses (first 11 from tagged texts)
1. (102) reduce, cut down, cut back, trim, trim down, trim back, cut, bring down -- (cut down on;
make a reduction in; "reduce your daily fat intake"; "The employer wants to cut back health
benefits")
2. (9) reduce -- (make less complex; "reduce a problem to a single question")
3. (5) reduce -- (bring to humbler or weaker state or condition; "He reduced the population to
slavery")
4. (3) reduce -- (simplify the form of a mathematical equation of expression by substituting one
term for another)
5. (3) reduce -- (lower in grade or rank or force somebody into an undignified situation; "She
reduced her niece to a servant")
6. (3) reduce, come down, boil down -- (be the essential element; "The proposal boils down to a
compromise")
7. (2) shrink, reduce -- (reduce in size; reduce physically; "Hot water will shrink the sweater";
"Can you shrink this image?")
8. (1) reduce -- (lessen and make more modest; "reduce one's standard of living")
9. (1) reduce, scale down -- (make smaller; "reduce an image")
10. (1) deoxidize, deoxidise, reduce -- (to remove oxygen from a compound, or cause to react with
hydrogen or form a hydride, or to undergo an increase in the number of electrons)
11. (1) reduce, tighten -- (narrow or limit; "reduce the influx of foreigners")
12. repress, quash, keep down, subdue, subjugate, reduce -- (put down by force or intimidation; "The
government quashes any attempt of an uprising"; "China keeps down her dissidents very efficiently";
"The rich landowners subjugated the peasants working the land")
13. reduce -- (undergo meiosis; "The cells reduce")
14. reduce -- (reposition (a broken bone after surgery) back to its normal site)
15. reduce -- (destress and thus weaken a sound when pronouncing it)
16. abridge, foreshorten, abbreviate, shorten, cut, contract, reduce -- (reduce in scope while
retaining essential elements; "The manuscript must be shortened")
17. boil down, reduce, decoct, concentrate -- (be cooked until very little liquid is left; "The
sauce should reduce to one cup")
18. reduce, boil down, concentrate -- (cook until very little liquid is left; "The cook reduced the
sauce by boiling it for a long time")
19. dilute, thin, thin out, reduce, cut -- (lessen the strength or flavor of a solution or mixture;
"cut bourbon")
20. reduce, melt off, lose weight, slim, slenderize, thin, slim down -- (take off weight)
Overview of adj reduced
The adj reduced has 2 senses (first 2 from tagged texts)
1. (6) decreased, reduced -- (made less in size or amount or degree)
2. (1) reduced, rock-bottom -- (well below normal (especially in price))
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